Efficient Control of Zika Virus Infection Induced by a Non-Replicating Adenovector Encoding Zika Virus NS1/NS2 Antigens Fused to the MHC Class II-Associated Invariant Chain.

Loulieta Nazerai,Anette Stryhn,Allan Randrup Thomsen,Jan Pravsgaard Christensen,Søren Buus

doi:10.3390/v13112215

Abstract

It is generally believed that a successful Zika virus (ZIKV) vaccine should induce neutralizing antibodies against the ZIKV envelope (E) protein to efficiently halt viral infection. However, E-specific neutralizing antibodies have been implicated in a phenomenon called antibody-dependent enhancement, which represents an ongoing concern in the flavivirus-vaccinology field. In this report, we investigated the vaccination potential of replication-deficient adenoviral vectors encoding the ZIKV non-structural proteins 1 and 2 (NS1/NS2) and employed the strategy of linking the antigens to the MHC-II associated invariant chain (li) to improve immunogenicity and by inference, the level of protection. We demonstrated that li-linkage enhanced the production of anti-NS1 antibodies and induced an accelerated and prolonged polyfunctional CD8 T cell response in mice, which ultimately resulted in a high degree of protection against ZIKV infection of the CNS.

Highlights

The severe clinical consequences of Zika virus (ZIKV) infection including microcephaly in newborns and Guillain–Barre syndrome in adults, highlight the pressing need for a protective vaccine
We show that: (I) vaccination with Ad-liNS1/NS2 is able to confer increased levels of protection against subsequent intracranial (i.c.) ZIKV challenge in immunocompetent adult mice; (II) li-linkage enhances the production of anti-NS1 antibodies and induces an accelerated ZIKV-specific CD8 T cell response that is sustained in vaccinated mice at high levels for an extended period of time; and (III) polyfunctional
Given that the population receiving the ZIKV vaccine will include pregnant women, it is critical that the vaccine is non-replicating, but still immunogenic

Summary

Introduction

The severe clinical consequences of Zika virus (ZIKV) infection including microcephaly in newborns and Guillain–Barre syndrome in adults, highlight the pressing need for a protective vaccine. The viral genome contains one open reading frame encoding a single polypeptide, which is subsequently cleaved into three structural proteins, (capsid (C), premembrane/membrane (prM/M), and envelope (E)), and seven non-structural proteins, ZIKV is generally quite genetically homogenous, and an African and Asian lineage is distinguished, all variants seem to belong to a single serotype [3], suggesting that one vaccine should suffice for general protection. There are currently no licensed human vaccines, but a handful has reached initial clinical evaluation including purified inactivated ZIKV as well as DNA, mRNA, and vector-based vaccines carrying the prM/E proteins [4,5]. Studies performed in animal models suggest that neutralizing antibodies (nAbs) targeting the E protein on the viral surface play a primary role in protection [5,6]

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Results

Conclusion